J.C. Holstege (Joan)http://repub.eur.nl/ppl/5596/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryUnacylated ghrelin suppresses grelin-induced neuronal activity in the hypothalamus and brainstem of male ratshttp://repub.eur.nl/pub/60383/
Thu, 22 May 2014 00:00:01 GMT<div>D.M. Stevanovic</div><div>A. Grefhorst</div><div>A.P.N. Themmen</div><div>V. Popovic</div><div>J.C. Holstege</div><div>E.D. Haasdijk</div><div>M. Trajkovic</div><div>A.J. van der Lely</div><div>P.J.D. Delhanty</div>
Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular administration of AG, UAG and their combination (AG+UAG) to young adult Wistar rats on food intake and central melanocortin system modulation. Although UAG did not affect food intake it significantly increased the number of c-Fos positive neurons in the arcuate (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination treatments caused activation of c-Fos in POMC expressing neurons in the arcuate, substantiating a physiologic effect of these peptides on the central melanocortin system. Together, these results demonstrate that UAG can act directly to increase neuronal activity in the hypothalamus and is able to counteract AG-induced neuronal activity in the PVN and NTS. UAG also modulates expression of members of the melanocortin signaling system in the hypothalamus. In the absence of an effect on energy intake, these findings indicate that UAG could affect energy homeostasis by modulation of the central melanocortin system.Thermo-sensitive TRP channels in peripheral nerve injury: A review of their role in cold intolerancehttp://repub.eur.nl/pub/66462/
Wed, 01 Jan 2014 00:00:01 GMT<div>S. Kambiz</div><div>L.S. Duraku</div><div>J.C. Holstege</div><div>S.E.R. Hovius</div><div>T.J.H. Ruigrok</div><div>E.T. Walbeehm</div>
One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels.Differential distribution of activated spinal neurons containing glycine and/or GABA and expressing c-fos in acute and chronic pain modelshttp://repub.eur.nl/pub/20973/
Mon, 01 Nov 2010 00:00:01 GMT<div>S.M. Hossaini</div><div>L.S. Duraku</div><div>C. Saraç</div><div>J.L.M. Jongen</div><div>J.C. Holstege</div>
The inhibitory transmitters GABA and glycine play an important role in modulating pain transmission, both in normal and in pathological situations. In the present study we have combined in situ hybridization for identifying spinal neurons that use the transmitter(s) glycine and/or GABA (Gly/GABA neurons) with immunohistochemistry for c-fos, a marker for neuronal activation. This procedure was used with acute pain models induced by the injection of capsaicin or formalin; and chronic pain models using Complete Freund's Adjuvant (CFA, chronic inflammation), and the spared nerve injury (SNI) model (neuropathic pain). In all models Gly/GABA neurons were activated as indicated by their expression of c-fos. The pattern of Gly/GABA neuronal activation was different for every model, both anatomically and quantitatively. However, the averaged percentage of activated neurons that were Gly/GABA in the chronic phase (≥20 h survival, 46%) was significantly higher than in the acute phase (≤2 h survival, 34%). In addition, the total numbers of activated Gly/GABA neurons were similar in both phases, showing that the activation of non-Gly/GABA (presumed excitatory) neurons in the chronic phase decreased. Finally, morphine application equally decreased the total number of activated neurons and activated Gly/GABA neurons. This showed that morphine did not specifically activate Gly/GABA neurons to achieve nociceptive inhibition. The present study shows an increased activity of Gly/GABA neurons in acute and chronic models. This mechanism, together with mechanisms that antagonize the effects of GABA and glycine at the receptor level, may determine the sensitivity of our pain system during health and disease.The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndromehttp://repub.eur.nl/pub/55151/
Thu, 01 May 2003 00:00:01 GMT<div>R. Willemsen</div><div>M. Hoogeveen-Westerveld</div><div>S. Reis</div><div>J.C. Holstege</div><div>E.A.W.F.M. Severijnen</div><div>I.M. Nieuwenhuizen</div><div>M. Schrier</div><div>L. van Unen</div><div>F. Tassone</div><div>A.T. Hoogeveen</div><div>P.J. Hagerman</div><div>E.J. Mientjes</div><div>B.A. Oostra</div>
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndromehttp://repub.eur.nl/pub/10126/
Wed, 01 Jan 2003 00:00:01 GMT<div>R. Willemsen</div><div>L. van Unen</div><div>F. Tassone</div><div>B.A. Oostra</div><div>A.T. Hoogeveen</div><div>E.J. Mientjes</div><div>P.J. Hagerman</div><div>M. Hoogeveen-Westerveld</div><div>S. Reis</div><div>J.C. Holstege</div><div>E.A.W.F.M. Severijnen</div><div>I.M. Nieuwenhuizen</div><div>M. Schrier</div>
Recent studies have reported that alleles in the premutation range in the
FMR1 gene in males result in increased FMR1 mRNA levels and at the same
time mildly reduced FMR1 protein levels. Some elderly males with
premutations exhibit an unique neurodegenerative syndrome characterized by
progressive intention tremor and ataxia. We describe neurohistological,
biochemical and molecular studies of the brains of mice with an expanded
CGG repeat and report elevated Fmr1 mRNA levels and intranuclear
inclusions with ubiquitin, Hsp40 and the 20S catalytic core complex of the
proteasome as constituents. An increase was observed of both the number
and the size of the inclusions during the course of life, which correlates
with the progressive character of the cerebellar tremor/ataxia syndrome in
humans. The observations in expanded-repeat mice support a direct role of
the Fmr1 gene, by either CGG expansion per se or by mRNA level, in the
formation of the inclusions and suggest a correlation between the presence
of intranuclear inclusions in distinct regions of the brain and the
clinical features in symptomatic premutation carriers. This mouse model
will facilitate the possibilities to perform studies at the molecular
level from onset of symptoms until the final stage of the disease.Brainstem projections to motoneurons in the lumbar spinal cord : an ultrastructural study in rathttp://repub.eur.nl/pub/50937/
Wed, 04 Oct 1989 00:00:01 GMT<div>J.C. Holstege</div>
This thesis deals with an ultrastructural study
in rat on the descending projections from the
ventro-lateral medullary medial reticular formation,
the medullary raphe nuclei and the
area of the nucleus coeruleus and subcoeruleus
to the motoneuronal cell groups in the
lumbar spinal cord. Since these projections
te~inate not only in the intermediate zone,
bu~ also directly on motoneurons, they constitute
a special subgroup of the descending
pathways to the spinal cord (reviewed briefly
in Ch I.5).